Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analyzed the regulation and expression of ASPP members, genes implicated in the regulation of the apoptotic function of the TP53 tumor-suppressor gene, in acute lymphoblastic leukemia (ALL). Expression of ASPP1 was significantly reduced in ALL and was dependent on hypermethylation of the ASPP1 gene promoter. Abnormal ASPP1 expression was associated with normal function of the tumor-suppressor gene TP53 in ALL. The analyses of 180 patients with ALL at diagnosis showed that the ASPP1 promoter was hypermethylated in 25% of cases with decreased mRNA expression. Methylation was significantly higher in adult ALL vs childhood ALL (32 vs 17%, P = 0.03) and T-ALL vs B-ALL (50 vs 9%, P = 0.001). Relapse rate (62 vs 44%, P = 0.05) and mortality (59 vs 43%, P = 0.05) were significantly higher in patients with methylated ASPP1. DFS and OS were 32.8 and 33.7% for patients with unmethylated ASPP1 and 6.1 and 9.9% for methylated patients (P < 0.001 y P < 0.02, respectively). On the multivariate analysis, methylation of the ASPP1 gene promoter was an independent poor prognosis factor in ALL patients. Our results demonstrate that decreased expression of ASPP1 in patients with ALL is due to an abnormal methylation of its promoter and is associated with a poor prognosis.
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PMID:ASPP1, a common activator of TP53, is inactivated by aberrant methylation of its promoter in acute lymphoblastic leukemia. 1631 41

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.
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PMID:[Influence of the delay between conservative surgery and radiation therapy on local relapse in node-positive breast tumor]. 1656 18

As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.
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PMID:Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? 1738 30

The treatment of node-positive breast cancer has improved dramatically in the last 3 decades. Adjuvant therapies have evolved from single-agent chemotherapy to anthracycline- and taxane-based polychemotherapeutics to target-specific trastuzumab, with or without endocrine manipulation and with or without PMRT. Almost 85% of patients who have node-positive disease can now enjoy a 5-year DFS. This progress has come from incremental improvements made over the years. In spite of these advances, lingering questions remain. Is it possible to reduce treatment-associated toxicity? Can patient selection be improved based on tumor genomic profiling? Given the high cost of many of these therapies (37,000 dollars with the newer agents versus $391 for the classic six cycles of intravenous CMF), is it possible to achieve equivalent efficacy and yet reduce the economic cost per patient? Only continued clinical trials and cooperative effort among researchers, clinicians, and patients can answer these questions and improve care for breast cancer.
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PMID:Adjuvant therapy for patients who have node-positive breast cancer. 1716 96

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.
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PMID:Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors. 1735 96

The heterogeneity of the evolution of breast cancer complicates patient management. The use of vascular markers as prognostic factors is a new and promising tool in medical oncology. Research data of the current decade demonstrate that angiogenesis plays substantial role in growth and spread of malignant tumor. At present, immunohistochemical determination of intratumoral microvascular density represents one of the more promising new prognostic indicators in breast cancer that needs to be further investigated to identify and standardize the method of choice to be tested in prospective clinical studies. Consequently markers of angiogenic activity have receiving increasing attention. By analyzing the evolution of 209 cases of breast cancer enrolled in a prospective study reaching the 5th year of follow up, we provide herein data supporting that Factor VIII and CD34 could be reliable markers for prognosis of DFS. Tumors with lower expression of Factor VIII and CD34 have a better prognostic and lower potential metastatic. The Factor VIII comparative with CD34 represents a more faithful prognostic marker. Angiogenesis markers have also become a putative therapeutic target.
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PMID:[Vascular molecular markers for determination of disease free survival (DFS) of breast cancer]. 1743 6

Somatic mutations and large-scale depletion in mitochondrial DNA (mtDNA) have been extensively detected in various human cancers. However, it still remains unclear whether the alterations in mtDNA content are related to the clinicopathological parameters and patient prognosis in breast cancer. In the present study, we analyzed the copy number of mtDNA in 59 cases of invasive breast tumors and paired nontumorous tissues using quantitative real-time PCR. Our data showed that the level of mtDNA was significantly decreased in tumor tissues as compared to the adjacent nontumorous counterparts (P = 0.001). The reduced copy number in mtDNA was associated with an older onset age (>or=50 years old, P = 0.035) as well as a higher histological grade (P = 0.012). Survival analysis measured by the Kaplan-Meier curves and the log-rank test indicated that patients with reduced mtDNA content had significantly poorer disease-free survival (DFS, P = 0.0079) and overall survival (OS, P = 0.011) rate. In addition, tumors harboring mutations in displacement (D)-loop region, particularly at the polycytidine stretch (T/N ratio = 64.3 +/- 8.2%) or close to the replication origins of the heavy-strand (T/N ratio = 68.7 +/- 5.5%), had a significantly lower copy number of mtDNA than the ones without D-loop alterations. Together, our results suggested that reduced copy number of mtDNA may be involved in breast neoplastic transformation or progression and mtDNA content might be potentially used as a tool to predict prognosis. Somatic mutation in the D-loop region probably is one of key contributing factors leading to decreased mtDNA level in breast tumors.
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PMID:Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. 1765 21

82 patients with adenolymphoma of parotid gland treated with surgery in Department of Oncological Surgery Cancer Center, Gliwice in the period of 1986-2004 were retrospectively analyzed. They were about 22% of all patients with parotid gland tumors operated in that period. In almost 70% of cases partial parotidectomy with facial nerve preservation was performed as a treatment of choice. In that group DFS was over 95%. Local recurrence occurred in less then 5%, only in cases with multiple tumor in histopathological examinations. Quality of life parameters were also analyzed. In the analysis complications rate increased with the extension of surgical treatment. It revealed in the postoperative cosmetic defect evaluation. Partial resection of the parotid gland could be useful method of surgical treatment of adenolymphoma selected cases. It allows to achieve the same results as classic parotidectomy with lower risk of significant complications. In analyzed group the local recurrence was always combined with multi lesional growth of the tumor.
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PMID:[Partial parotidectomy--alternative method in surgical management of parotid gland Warthin tumours]. 1766 99

It is common belief that patients failing chemoradiation therapy (CRT) for squamous cell cancer of the anus (SCCA) can be salvaged with subsequent surgery. The aim of this study was to examine our experience with abdominoperineal resection (APR) in cases of persistent or recurrent SCCA with an emphasis on survival and morbidity. All patients between 1985 and 2001 undergoing salvage APR were reviewed. Details of CRT, surgery, tumor characteristics, postoperative complications, and survival were obtained from medical records. There were 22 patients (13 women, 9 men) with a mean age of 62 years (range=42-87). Initial tumors were AJCC stage 2 (16 cases), 3A (3 cases), and 4 (1 case). Mean radiation dose was 47.6 Gy (30-60) and most received concomitant 5-FU. In 20 patients, APR was felt to be "curative" but only 13 (65%) had negative margins on final pathology. Thirteen (59%) perineal wounds broke down with a median time to healing of 7 months. Tumor differentiation (p=0.02) and positive resection margins (p=0.004) were significantly associated with DFS (5-year DFS of 37%). Salvage APR in patients with poorly differentiated tumors or positive resection margins has a high morbidity and poor survival and may warrant a planned APR after CRT instead.
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PMID:Salvage surgery after failed chemoradiation for anal canal cancer: should the paradigm be changed for high-risk tumors? 1784 56

YKL-40 is a new biomarker in serum with a prognostic value in several localized and metastatic malignancies. The current knowledge regarding the biological functions of YKL-40 in cancer links YKL-40 to increased aggressiveness of the tumor. Utilizing tissue microarrays, YKL-40 protein expression in tumor tissue was assessed by immunohistochemistry in a cohort of 630 high-risk breast cancer patients with a median estimated potential follow-up time of 10 and 13 years for disease-free (DFS) and overall survival (OS), respectively. YKL-40 protein expression was found in malignant tumor cells and in inflammatory cells. High expression was associated with positive estrogen and progesterone receptor status and high tumor differentiation. Contrary to studies on serum YKL-40 as a prognostic biomarker, a high YKL-40 expression in tumor cells was not significantly associated with DSF and OS in univariate and multivariate analyses.
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PMID:YKL-40 protein expression is not a prognostic marker in patients with primary breast cancer. 1815 33


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